G-CSF instillation into rat lungs mediates neutrophil recruitment, pulmonary edema, and hypoxia.
Activated neutrophils (PMN) have been implicated in the pathogenesis of adult respiratory distress syndrome (ARDS). Granulocyte colony-stimulating factor (G-CSF) is essential for PMN production and activation of PMN functions. We have recently shown that levels of G-CSF mRNA in a rat model of hemorrhagic shock correlated with severity of shock, PMN infiltration, pulmonary edema, and hypoxia. To determine whether increased tissue levels of G-CSF contribute to PMN recruitment and PMN-mediated injury, we instilled G-CSF into the lungs by intratracheal injection. Animals treated with G-CSF became hypoxic, hypocapnic, and alkalotic and demonstrated increased BAL fluid cellularity compared with control animals. The wet-to-dry ratio increased significantly after G-CSF instillation and peaked at 12 h. Histological examination of the lungs from G-CSF-treated rats revealed marked edema and increased PMN within the interstitium and alveoli. These results indicate that the presence of G-CSF alone in the lung can lead to recruitment of PMN, lung injury, and impaired pulmonary function, suggesting that local production of G-CSF may contribute to the development of lung damage and possibly ARDS in the setting of resuscitated hemorrhagic shock.
Hierholzer
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C
Department of Surgery, University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Kelly
E
E
Lyons
V
V
Roedling
E
E
Davies
P
P
Billiar
T R
TR
Tweardy
D J
DJ
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D000860:Hypoxia / Q000139:chemically induced; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000473:pathology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000503:physiopathology*; D014132:Trachea
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D009195:Peroxidase